What are the diagnostic tests for hepatitis C virus and how are they used to diagnose hepatitis C infection?
Several diagnostic tests currently are available for the
diagnosis of HCV infection.
They can be categorized according to the way the tests are used.
Screening tests
Screening tests are tests that are used to diagnose a
condition or disease among individuals not known to have the disease. They are is
particularly useful for individuals who have risk factors for the condition or
disease.
The first step in screening for HCV infection is to test blood for the antibody
to HCV using an enzyme immuno-assays (EIAs). If the EIA test is negative (does
not find the antibody), the patient is assumed to be free of HCV. It takes
several weeks (up to six months) for antibodies to develop after the initial
infection with HCV, so this screening test may miss a few newly-infected
individuals. The EIA screening tests are very good (specific); if the test is
positive the probability of having HCV infection is greater than 99%.
Recombinant immunoblot assay (RIBA) is used to confirm the positive results
of EIAs since occasionally a positive EIA is a false positive, that is, the test
is positive when HCV is not present. Although the direct detection of HCV RNA
(HCV PCR) also is widely used to confirm the HCV infection, RIBA is still useful
to differentiate false positive results in the few individuals whose immune
systems have eliminated the virus but still have antibodies left over from the
resolved infection.
As previously described, HCV contains RNA. Several tests (assays) are
available to measure the amount of HCV RNA in a person's blood. These tests are
referred to as molecular tests because they examine the virus at the molecular
level. A single negative test for RNA does not mean that there is no infection
because the virus may appear in the blood intermittently or may exist in small
amounts. Newer tests have helped by detecting smaller and smaller amounts of
virus in the blood.
Testing for RNA is useful in determining whether or not a patient has
circulating virus in the blood (viremia). Hence, it can be used to confirm that
a positive EIA/ELISA truly reflects active HCV infection.
RNA testing also should be done in individuals who may have been recently
exposed to HCV. HCV RNA testing is more sensitive (that is, will detect more
cases) than the conventional EIA testing in this setting. The reason for this
greater sensitivity is that it may take a person several weeks after exposure to
HCV to develop the antibodies, whereas HCV RNA becomes detectable one to three
weeks after exposure. Finally, HCV RNA testing may be helpful to assess a
patient's response to treatment at certain time points during antiviral therapy
(see treatment of HCV below).
Blood tests also have been developed to identify the HCV genotype. This
information is used to help guide treatment.
The table below provides guidelines for interpreting the results of testing
for HCV antibodies by EIA and RIBA and for hepatitis C virus RNA. These are
standard interpretations, but it is important to remember that the diagnosis of
HCV infection should be made by an experienced clinician who is familiar with
the patient's medical history.
| Anti-HCV (ELISA/EIA) |
Anti-HCV (RIBA) |
HCV RNA |
Interpretation |
| Negative |
Negative |
Negative |
No infection |
| Positive |
Positive |
Positive |
Ongoing infection |
| Positive |
Positive |
Negative |
Past or current infection. Additional or repeat testing should be done
to exclude fluctuating or low levels of viremia. |
| Positive |
Negative |
Negative |
False positive ELISA; no infection |
| Positive |
Indeterminate |
Negative |
Situation unclear, consider additional testing |
| Negative |
Negative |
Positive |
New (acute) HCV infection or chronic HCV infection in an
immunocompromised person unable to make adequate antibodies. |